Antigen binding constructs to CD8

Abstract

Antigen binding constructs that bind to CD8, for example antibodies, including antibody fragments (such as scFv, minibodies, and cys-diabodies) that bind to CD8, are described herein. Methods of use are described herein.

We claim: 
     
       1. A antigen binding construct that comprises:
 a variable heavy (V H ) domain comprising:
 a HCDR1 of a HCDR1 of SEQ ID NO: 3 or 6; 
 a HCDR2 of HCDR2 of SEQ ID NO: 3 or 6; 
 a HCDR3 of HCDR3 of SEQ ID NO: 3 or 6; 
 a HFR3 of a HFR3 of SEQ ID NO: 48; and 
 
 a variable light (V L ) domain comprising:
 a LCDR1 of LCDR1 of SEQ ID NO: 9; 
 a LCDR2 of LCDR2 of SEQ ID NO: 9; and 
 a LCDR3 of LCDR3 of SEQ ID NO: 9. 
 
 
     
     
       2. The antigen binding construct of  claim 1 , wherein the antigen binding construct binds specifically to CD8. 
     
     
       3. The antigen binding construct of  claim 1 , further comprising a detectable marker. 
     
     
       4. The antigen binding construct of  claim 1 , further comprising a therapeutic agent. 
     
     
       5. The antigen binding construct of  claim 1 , wherein the antigen binding construct is bispecific. 
     
     
       6. The antigen binding construct of  claim 1 , wherein the antigen binding construct is a monovalent scFv. 
     
     
       7. A cys-diabody that binds to CD8, the cys-diabody comprising a polypeptide that comprises:
 a single-chain variable fragment (scFv) comprising a variable heavy (V H ) domain linked to a variable light (V L ) domain; and 
 the V H  domain comprising:
 a HCDR1 of a HCDR1 of SEQ ID NO: 3 or 6; 
 a HCDR2 of a HCDR2 of SEQ ID NO: 3 or 6; 
 a HCDR3 of a HCDR3 of SEQ ID NO: 3 or 6; and 
 a HFR3 of a HFR3 of SEQ ID NO: 48; and 
 
 the V L  domain comprising:
 a LCDR1 of LCDR1 of SEQ ID NO: 9; 
 a LCDR2 of a LCDR2 of SEQ ID NO: 9; and 
 a LCDR3 of a LCDR3 of SEQ ID NO: 9. 
 
 
     
     
       8. The cys-diabody of  claim 7 , wherein the order of the variable domains, from N terminus to C terminus of the polypeptide is V L , V H . 
     
     
       9. The cys-diabody of  claim 7 , wherein the order of the variable domains, from N terminus to C terminus of the polypeptide is V H , V L . 
     
     
       10. The cys-diabody of  claim 7 , further comprising a detectable molecule. 
     
     
       11. A minibody that binds to CD8, the minibody comprising a polypeptide that comprises from N-terminus to C-terminus:
 a single-chain variable fragment (scFv) that binds to CD8, the scFv comprising a variable heavy (V H ) domain linked to a variable light (V L ) domain,
 the V H  domain comprising:
 a HCDR1 of SEQ ID NO: 48; 
 a HCDR2 of SEQ ID NO: 48; 
 a HCDR3 of SEQ ID NO: 48; 
 a HFR3 of a HFR3 of SEQ ID NO: 48; and 
 
 the V L  domain comprising:
 a LCDR1 of SEQ ID NO: 42; 
 a LCDR2 of SEQ ID NO: 42; and 
 a LCDR3 of SEQ ID NO: 42; 
 
 
 a hinge-extension domain comprising a IgG1 hinge region; and 
 a IgG C H 3 sequence. 
 
     
     
       12. The minibody of  claim 11 , further comprising a detectable marker. 
     
     
       13. A kit comprising:
 an antigen binding construct of  claim 1 ; and 
 a detectable marker. 
 
     
     
       14. The cys-diabody of  claim 7 , further comprising:
 a therapeutic agent; and 
 a cysteine tail comprising a disulfide linkage with the therapeutic agent. 
 
     
     
       15. The minibody of  claim 11 , wherein the V H  domain is a V H  domain of SEQ ID NO: 48, and wherein the V L  domain is a V L  domain of SEQ ID NO: 42. 
     
     
       16. The minibody of  claim 11 , wherein the minibody is humanized. 
     
     
       17. The antigen binding construct of  claim 1 , wherein the antigen binding construct is humanized. 
     
     
       18. The antigen binding construct of  claim 1 , wherein the V H  domain is a V H  domain of SEQ ID NO: 48, and wherein the V L  domain is a V L  domain of SEQ ID NO: 42. 
     
     
       19. The antigen binding construct of  claim 1 , wherein the antigen binding construct is an antibody. 
     
     
       20. The antigen binding construct of  claim 1 , wherein the variable heavy (V H ) domain comprises:
 the amino acid sequence of positions 26-31 of SEQ ID NO: 48; 
 the amino acid sequence of positions 50-58 of SEQ ID NO: 48; 
 the amino acid sequence of positions 99-107 of SEQ ID NO: 48; and 
 the amino acid sequence of positions 59-98 of SEQ ID NO: 48; and 
 the variable light (V L ) domain comprises: 
 the amino acid sequence of positions 24-34 of SEQ ID NO: 42; 
 the amino acid sequence of positions 50-56 of SEQ ID NO: 42; and 
 the amino acid sequence of positions 89-97 of SEQ ID NO: 42.